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Original article:
Xiaoyong Jin1,Zheng Liu2,Baojian Guo1,Gaoxiao Zhang2,Zaijun Zhang2,Lipeng Xu2,Yuqiang Wang2,Yewei Sun2*
1 Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy,Guangzhou, 510632, China
2 Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy, Guangzhou, 510632, China
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*Yewei Sun, Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy,Guangzhou, 510632, China
Article citation: Jin X, Liu Z, Guo B,Zhang G, Zhang Z, Xu L, Wang Y, Sun Y. A promising dual-functional neuroprotective derivative of memantine. J Pharm Biomed Sci 2016;06(06):392–398.Available at www.jpbms.info
ABSTRACT
Background Memantine, an open-channel, uncompetitive blocker of NMDA receptors, is a major treatment for moderate-to-severe Alzheimer’s disease. The NMDA receptor activity can also be inhibited allosterically by S-nitrosylation of Cys residues, a redox-mediated chemical reaction.
Aim To enhance the inhibitory effect of memantine on NMDA receptors and its neuroprotective effect. Settings and Design In this study, we designed and synthesized a memantine nitrate compound (MN-2, also known as YQW-035), with the potential for both allosteric and direct uncompetitive blockade. Then, the protective effects of MN-2 were evaluated both in vitro and in vivo.
Results and Conclusions Biological evaluations demonstrated that MN-2 showed a stronger protective effect in cultured neuronal cells and in a rat transient stroke model compared with memantine. The mechanism underlying the action of MN-2 may be attributed to its dual inhibition of NMDA receptors. These results suggested MN-2 has promising potential for treatment of various neurological disorders characterized by overstimulation of NMDA receptors.
KEYWORDS memantine nitrate, neurological disorder, NMDA receptor, S-nitrosylation
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